Drug information of Simvastatin

Mechanism of effect

Simvastatin is a prodrug and is hydrolyzed to its active β-hydroxyacid form, Simvastatin acid, after administration. Simvastatin is a specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, an early and rate limiting step in the biosynthetic pathway for cholesterol. In addition, Simvastatin reduces VLDL and TG and increases HDL-C.

Pharmacodynamic

Simvastatin is an oral antilipemic agent which inhibits HMG-CoA reductase.

Pharmacokinetics

Since Simvastatin undergoes extensive first-pass extraction in the liver, the availability of the drug to the general circulation is low (<5%). Both Simvastatin and its β-hydroxyacid metabolite are highly bound (approximately 95%) to human plasma proteins. Peak plasma concentrations of both active and total inhibitors were attained within 1.3 to 2.4 hours postdose. Following an oral dose of 14C-labeled Simvastatin in man, 13% of the dose was excreted in urine and 60% in feces.

Drug indications

Hyperlipidemia , Heterozygous Familial Hypercholesterolemia , Homozygous Familial Hypercholesterolemia , Prevention of Cardiovascular Disease

Dosage

Usual Adult Dose for Prevention of Cardiovascular Disease Usual dosage range: 5 to 40 mg orally once a day in the evening Usual Adult Dose for Cardiovascular Risk Reduction Usual dosage range: 5 to 40 mg orally once a day in the evening Usual Adult Dose for Homozygous Familial Hypercholesterolemia Recommended dose: 40 mg orally once a day in the evening Usual Pediatric Dose for Heterozygous Familial Hypercholesterolemia Less than 10 years: Not recommended 10 years or older: Initial dose: 10 mg orally once a day in the evening Maintenance dose: 10 to 40 mg orally once a day in the evening Maximum dose: 40 mg orally once a day in the evening

Drug contraindications

Pregnancy , Lactation , hypersensitivity to drug or its components. , Active liver disease

Side effects

Headache , insomnia , constipation , abdominal pain , vertigo , Urinary tract infection , edema , sinusitis , myalgia , gastritis , bronchitis , diabetes mellitus , atrial fibrillation

Interactions

Amlodipine/Atorvastatine , Imatinib , Bleomycin , Bosentan , Ranitidine , Repaglinide , Zafirlukast , Cyproterone acetate , Amlodipine , Amiodarone , Erythromycin , Posaconazole , Gemfibrozil , Danazol , Diltiazem , Verapamil , Voriconazole , Ketoconazole , Clarithromycin , Cyclosporine , Fenofibrate , Libidox , Heracles , Clofibrate , Diltigel , Rifabutin , Rifapentine , Ranolazine , Darunavir , Nefazodone , ritonavir , saquinavir , nelfinavir , Prednisolone , Mifepristone , Telithromycin , Indinavir , Daptomycin , Telmisartan , Tipranavir , Etravirine , Eltrombopag , Darifenacin , Mibefradil , cobicistat , Delavirdine , Oxiconazole , Butabarbital , Lopinavir and Ritonavir , ELBASVIR/GRAZOPREVIR , Lorlatinib , Troleandomycin , Nitrendipine , riociguat , tucatinib , Ombitasvir, Paritaprevir, and Ritonavir

Alerts

1-Simvastatin occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (ULN). 2-Women of childbearing age should be advised to use an effective method of birth control to prevent pregnancy while using Simvastatin. 3-Liver Dysfunction may occure. 4-The drug should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease.

Points of recommendation

1-Lipid determinations should be performed after 4 weeks of therapy and periodically thereafter. 2-Due to the increased risk of myopathy (including rhabdomyolysis), particularly during the first year of treatment, use of the 80 mg dose should be restricted to patients who have been taking 80 mg for 12 months or more without evidence of muscle toxicity.

Pregnancy level

X

Related drugs

Atorvastatin , Lovastatin , Rosuvastatin , Pitavastatin , pravastatin , fluvastatin , triparanol , bempedoic acid